膀胱尿路上皮癌中HER2基因扩增及蛋白表达的意义
|
摘要
目的:探讨人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)在膀胱尿路上皮癌(urothelial carcinoma of bladder,UCB)组织中的表达及其临床意义。方法:应用免疫组织化学法及FISH检测HER2在76例膀胱尿路上皮细胞癌和30例正常膀胱黏膜组织标本中的表达情况,分析其与膀胱癌的各病理参数间的关系。结果:HER2在膀胱尿路上皮细胞癌组织中的阳性表达率为29.0%,显著高于正常膀胱黏膜组织的0,差异有统计学意义(P<0.05);HER2蛋白表达水平与膀胱尿路上皮细胞癌的肿瘤大小、肿瘤级别及浸润深度相关(P<0.05)。结论:HER2蛋白的过表达与人膀胱尿路上皮细胞癌的发生、发展相关。检测HER2的表达情况可能对预测膀胱尿路上皮细胞癌的预后及选择治疗方法具有重要价值。
Objective: To study the expression and clinical significance of human epidermal growth factor receptor-2( HER2) protein in urothelial carcinoma of bladder. Methods: Immunohistochemical Maxvison and fluorescence in situ hybridization were used to detect the expression of HER2 in urothelial carcinoma of bladder of 76 cases and normal bladder mucosa of 30 cases. The relationship between HER2 and every pathologic parameters of bladder urothelial cell carcinoma was analyzed statistically. Results: The positive expression rate of HER2 in bladder urothelial cell carcinoma was29. 0%. It was higher than that in normal bladder mucosa( P < 0. 05). The positive expression of HER2 in urothelial carcinoma of the bladder was associated with the size of tumor,grading of tumor and the depth of tumor invasion( P <0. 05). Conclusion: The over-expression of HER2 is related to the development of human bladder urothelial cell carcinoma. Detection of HER2 expression may have great value in predicting the prognosis and selecting treatment for bladder urothelial cell carcinoma.
Objective: To study the expression and clinical significance of human epidermal growth factor receptor-2( HER2) protein in urothelial carcinoma of bladder. Methods: Immunohistochemical Maxvison and fluorescence in situ hybridization were used to detect the expression of HER2 in urothelial carcinoma of bladder of 76 cases and normal bladder mucosa of 30 cases. The relationship between HER2 and every pathologic parameters of bladder urothelial cell carcinoma was analyzed statistically. Results: The positive expression rate of HER2 in bladder urothelial cell carcinoma was29. 0%. It was higher than that in normal bladder mucosa( P < 0. 05). The positive expression of HER2 in urothelial carcinoma of the bladder was associated with the size of tumor,grading of tumor and the depth of tumor invasion( P <0. 05). Conclusion: The over-expression of HER2 is related to the development of human bladder urothelial cell carcinoma. Detection of HER2 expression may have great value in predicting the prognosis and selecting treatment for bladder urothelial cell carcinoma.
引文
[1]Mejri N,Sellami R,Lamia C,et al.Status of HER2 over expression in muscle invasive urothelial bladder carcinoma:Report of 21 cases[J].Urol Ann,2014,6(1):63-7.
[2]韩苏军,张思维,陈万青,等.中国膀胱癌发病现状及流行趋势分析[J].癌症进展,2013,11(1):89-95.
[3]肖锋.HER2及其在膀胱癌中的意义[J].中国肿瘤外科杂志,2011,3(4):238-240.
[4]Matsubara H,Yamada Y,Naruse K,et al.Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma:comparative study of immunohistochemistry and fluorescent in situ hybridization[J].Oncol Rep,2008,19(1):57-63.
[5]Sven G,Stefan K,Oliver WH,et al.Different HER2 Protein Expression Profiles Aid in the Histologic Differential Diagnosis Between Urothelial Carcinoma In Situ(CIS)and Non-CIS Conditions(Dysplasia and Reactive Atypia)of the Urinary Bladder Mucosa[J].Am J Clin Pathol,2011,136(6):881-888.
[6]Latif Z,Watters AD,Dunn I,et al.HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder[J].Br J Cancer,2003,89(7):1305-1309.
[7]《乳腺癌HER2检测指南(2014版)》编写组.乳腺癌HER2检测指南(2014版)[J].中华病理学杂志,2014,43(4):262-267.
[8]Yarden Y,Sliwkowski M X.Untangling the Erb B signalling network[J].Nat Rev Mol Cell Biol,2001,2(2):127-137.
[9]Cho H S,Mason K,Ramyar K X,et al.Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab[J].Nature,2003,421(6924):756-760.
[10]Ono M,Kuwano M.Molecular mechanisms of epidermal growth factor receptor(EGFR)activation and response to gefitinib and other EGFRtargeting drugs[J].Clin Cancer Res,2006,12(24):7242-7251.
[11]包卿兵,刘军,林建中,等.表皮生长因子受体和HER2在膀胱移行上皮细胞癌中的过度表达和意义[J].山西医药杂志,2007,12(36):1089-1091.
[12]CAI CY,YAO Z.Activation of NF-kb in human breast cancer and its role in cell proliferation and progression[J].Chinese J Cllionncology,2006,3(1):5-10.
[13]JOHNSO CJ,BARRY MB,V ASEF MA,et al.Her2/neu expression in salivay duct carcinoma:an immunohistochemical and chromogenic in situ hybridization study[J].Appl Immunohistochem Mol Morphol,2008,16(1):54-58.
[14]俞平,杨兆瑞,路光中,等.乳腺癌Her-2/neu的免疫组织化学检测[J].中华病理学杂志,2003,32(5):479-481.
[15]Wrigh t C,A ngus B,Nicholson S,et al.Exp ressi on of cerb B-2 oncoprotein:a prognost ic indicat or in breas t cancer[J].Cancer Res,1999,49:2087.
[16]毛必静,张志敏,陈川,等.HER2在胃癌靶向治疗中的作用及意义[J].世界华人消化杂志,2014,22(1):31-38.
[17]Jorgensen JT.Role of human epidermal growth factor receptor 2 in gastric cancer:biological and pharmacological aspects[J].World J Gastroenterol,2014,20(16):4526-4535.
[18]邱学德,刘乔保,王田,等.酪氨酸激酶抑制剂PDl68393对HER2不同表达水平膀胱癌细胞株的作用研究[J].中华肿瘤防治杂志,2006,13(8):604-605.
[19]Peyromaure M,ScottéF,Amsellem-Ouazana D,et al.Trastuzumab(Herceptin)in metastatic transitional cell carcinoma of the urinary tract:report on six patients[J].Eur Urol,2005,48(5):771-775.
[20]Hussain MH,Mac Vicar GR,Petrylak DP,et al.Trastuzumab,paclitaxel,carboplatin,and gemcitabine in advanced human epidermal growth factor receptor-2/neu positive urothelial carcinoma:results of a multicenter phaseⅡNational Cancer Institute trial[J].J Clin Oncol,2007,25(16):2218-2224.
[21]Skagias L,Politi E,Karameris A,et al.Prognostic impact of HER2/neu protein in urothelial bladder cancer.Survival analysis of 80 cases and an overview of almost 20years'research[J].Journal of B.U.ON.:official journal of the Balkan Union of Oncology,2009,14:457-462.
[2]韩苏军,张思维,陈万青,等.中国膀胱癌发病现状及流行趋势分析[J].癌症进展,2013,11(1):89-95.
[3]肖锋.HER2及其在膀胱癌中的意义[J].中国肿瘤外科杂志,2011,3(4):238-240.
[4]Matsubara H,Yamada Y,Naruse K,et al.Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma:comparative study of immunohistochemistry and fluorescent in situ hybridization[J].Oncol Rep,2008,19(1):57-63.
[5]Sven G,Stefan K,Oliver WH,et al.Different HER2 Protein Expression Profiles Aid in the Histologic Differential Diagnosis Between Urothelial Carcinoma In Situ(CIS)and Non-CIS Conditions(Dysplasia and Reactive Atypia)of the Urinary Bladder Mucosa[J].Am J Clin Pathol,2011,136(6):881-888.
[6]Latif Z,Watters AD,Dunn I,et al.HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder[J].Br J Cancer,2003,89(7):1305-1309.
[7]《乳腺癌HER2检测指南(2014版)》编写组.乳腺癌HER2检测指南(2014版)[J].中华病理学杂志,2014,43(4):262-267.
[8]Yarden Y,Sliwkowski M X.Untangling the Erb B signalling network[J].Nat Rev Mol Cell Biol,2001,2(2):127-137.
[9]Cho H S,Mason K,Ramyar K X,et al.Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab[J].Nature,2003,421(6924):756-760.
[10]Ono M,Kuwano M.Molecular mechanisms of epidermal growth factor receptor(EGFR)activation and response to gefitinib and other EGFRtargeting drugs[J].Clin Cancer Res,2006,12(24):7242-7251.
[11]包卿兵,刘军,林建中,等.表皮生长因子受体和HER2在膀胱移行上皮细胞癌中的过度表达和意义[J].山西医药杂志,2007,12(36):1089-1091.
[12]CAI CY,YAO Z.Activation of NF-kb in human breast cancer and its role in cell proliferation and progression[J].Chinese J Cllionncology,2006,3(1):5-10.
[13]JOHNSO CJ,BARRY MB,V ASEF MA,et al.Her2/neu expression in salivay duct carcinoma:an immunohistochemical and chromogenic in situ hybridization study[J].Appl Immunohistochem Mol Morphol,2008,16(1):54-58.
[14]俞平,杨兆瑞,路光中,等.乳腺癌Her-2/neu的免疫组织化学检测[J].中华病理学杂志,2003,32(5):479-481.
[15]Wrigh t C,A ngus B,Nicholson S,et al.Exp ressi on of cerb B-2 oncoprotein:a prognost ic indicat or in breas t cancer[J].Cancer Res,1999,49:2087.
[16]毛必静,张志敏,陈川,等.HER2在胃癌靶向治疗中的作用及意义[J].世界华人消化杂志,2014,22(1):31-38.
[17]Jorgensen JT.Role of human epidermal growth factor receptor 2 in gastric cancer:biological and pharmacological aspects[J].World J Gastroenterol,2014,20(16):4526-4535.
[18]邱学德,刘乔保,王田,等.酪氨酸激酶抑制剂PDl68393对HER2不同表达水平膀胱癌细胞株的作用研究[J].中华肿瘤防治杂志,2006,13(8):604-605.
[19]Peyromaure M,ScottéF,Amsellem-Ouazana D,et al.Trastuzumab(Herceptin)in metastatic transitional cell carcinoma of the urinary tract:report on six patients[J].Eur Urol,2005,48(5):771-775.
[20]Hussain MH,Mac Vicar GR,Petrylak DP,et al.Trastuzumab,paclitaxel,carboplatin,and gemcitabine in advanced human epidermal growth factor receptor-2/neu positive urothelial carcinoma:results of a multicenter phaseⅡNational Cancer Institute trial[J].J Clin Oncol,2007,25(16):2218-2224.
[21]Skagias L,Politi E,Karameris A,et al.Prognostic impact of HER2/neu protein in urothelial bladder cancer.Survival analysis of 80 cases and an overview of almost 20years'research[J].Journal of B.U.ON.:official journal of the Balkan Union of Oncology,2009,14:457-462.